CHICAGO—Two studies presented at the ASCO Annual Meeting may help to energize the until recently often-overlooked field of fatigue.
In an open-label Phase III trial, researchers found that once weekly treatment with epoetin alfa may help to prevent chemotherapy-associated anemia and improve patients' quality of life.
Treatment with epoetin alfa was associated with a significant improvement in quality of life, an increase in hemoglobin levels, and a reduced need for transfusion.
And a second, pilot study suggests that higher initial dosing of epoetin alfa than is currently used for the treatment of chemotherapy-associated anemia may elicit a more rapid hemoglobin response, offering less frequent—and thus more convenient—maintenance dosing.
In the Phase III study of breast cancer patients undergoing chemotherapy, early administration of epoetin alfa maintained hemoglobin levels and significantly improved quality of life on both the Functional Assessment of Cancer Therapy-Anemia Scale (FACT-An) and the Cancer Linear Analogue Scale (CLAS), reported Jose Chang, MD, an oncologist at the Durham Regional Cancer Centre in Oshawa, Ontario.
The patients had significantly more energy and an increased ability to perform daily activities, the study showed.
In contrast, quality of life, as assessed by both scales, significantly deteriorated in patients randomized to receive best supportive care, said Dr. Chang, speaking on behalf of the Canadian Eprex Study Group.
The study, which was designed to test the hypothesis that maintaining breast cancer patients' hemoglobin levels at 12 g/dL throughout chemotherapy would improve their quality of life, randomized 350 breast cancer patients undergoing at least 12 weeks of chemotherapy to either 40,000 IU of epoetin alfa, subcutaneously, once-weekly or best supportive care, for 16 weeks.
Best supportive care was defined as the care given to patients while on chemotherapy, Dr. Chang said.
The baseline characteristics, including age, hemoglobin levels, menopausal status, estrogen receptor status, and disease stage, were similar among both groups, Dr. Chang said. About three fourths of patients in both groups were receiving anthracycline-based chemotherapy, he said.
Hemoglobin Response Improved
Epoetin alfa was effective in over 90% of patients, Dr. Chang reported, with only 9% of patients requiring an increase in dose and 29% actually having a dose reduction.
The patients in the epoetin alfa arm were 10 times more likely to maintain hemoglobin at target levels, the study showed, with 52% having levels of 12 g/dL or greater throughout the study period, compared with 5.17% of those in the best supportive care arm.
The results were similar when a more traditional definition of hemoglobin response was applied, Dr. Chang said, with 65% of epoetin alfa patients hitting a value of 12 g/dL at least once without transfusion during the trial, compared with 6.5% in the best supportive care arm.
The women taking epoetin alfa were also less likely to need a transfusion: 8.7%, compared with 23% in the best supportive care arm. The total number of transfusions was also less in the epoetin alfa arm: 49 vs. 149 in the best supportive care arm, the study showed.
Adverse events were generally similar among the two groups, with a few exceptions. The patients in the epoetin alfa arm were slightly more likely to have modest to severe granulocytopenia, nausea, or anorexia, perhaps reflecting the fact they got slightly more chemotherapy: an average of 5 cycles vs. 4.6 in the best supportive care arm, Dr. Chang said. Fever and anemia were more frequent in the best supportive care arm.
Higher initial dosing of epoetin alfa may elicit a more rapid hemoglobin response, offering less frequent maintenance dosing.
An interim survival analysis showed no difference between the two groups, he said.
The Bottom Line
“This is one of the first large randomized clinical trials looking at anemia prevention and hemoglobin maintenance,” Dr. Chang said, showing improvement in quality of life, increase in hemoglobin, and reduction in blood product transfusion.
“The study may suggest a paradigm shift in how we manage our breast cancer patients and when intervention should be entertained.”
Long-time fatigue researcher Jamie H. Von Roenn, MD, Professor of Medicine in the Division of Hematology/Oncology and Director of the Palliative Care & Home Hospice Program at Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center there, applauded the researchers for taking a preventive approach.
She noted that previous studies have suggested that quality of life starts to deteriorate when hemoglobin levels drop from 12 g/dL into the 10 g/dL to 12 g/dL range.
Since baseline hemoglobin levels were about 11.1 g/dL in the study, “it's not surprising that we see this significant improvement in quality of life with the improvement in hemoglobin,” she said. “But seeing it actually proven is rewarding.”
While the Canadian trial might be one of the first to show the role of epoetin alfa in prevention, its role in anemia treatment is already well established, noted Jeffrey Patton, MD, an oncologist at Tennessee Oncology in Nashville.
Studies have shown that conventional dosing of 40,000 IU of epoetin alfa once-weekly increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in anemic cancer patients receiving chemotherapy, he said. His team wanted to test the hypothesis that higher initial dosing may elicit a more rapid hemoglobin response and require less frequent maintenance dosing.
The 24-week open-label, nonrandomized, pilot study enrolled 20 patients receiving myelosuppressive chemotherapy with a baseline hemoglobin level of 11 g/dL or less; the mean hemoglobin level was 10.2 g/dL.
The patients were administered 60,000 IU of epoetin alfa once weekly for eight weeks; then, if hemoglobin levels had increased by 2 g/dL or more, the patients began a maintenance dose of 120,000 IU every 3 weeks, Dr. Patton said. If hemoglobin increased by more than 1.3 g/dL in any two-week period, the physicians could choose to lower the epoetin alfa dose to 40,000 once a week.
If hemoglobin increased to more than 15 g/dL, epoetin alfa was withheld until hemoglobin dropped to 13 g/dL and then resumed at 20,000 IU once a week.
Proof of Principle Proven
The strategy appeared to work. By Week 4, hemoglobin levels had increased by an average of 1.0 g/dL; by Week 8, they had increased 2.9 g/dL, Dr. Patton reported.
In the 11 patients who received maintenance epoetin alfa therapy, the hemoglobin gain was sustained, in the 13 g/dL range, throughout the 24-week trial, he said.
Epoetin alfa was well tolerated, Dr. Patton added. “This study shows proof of principle, and we can now move to larger-scale trials.”
Ortho-Biotech helped to fund both studies.
ECRI Assessment Concludes Herceptin May Delay Metastatic Breast Cancer Progression, Increase Survival
An evaluation by ECRI of published studies of trastuzumab (Herceptin) has concluded that when combined with chemotherapy, the treatment may slow tumor progression in some patients with metastatic breast cancer.
Studies suggest that by blocking tumor cell growth and inducing an immune system attack on the tumor, trastuzumab may improve tumor response rates, delay tumor progression, and increase median survival time by four to six months, with few adverse effects.
The drug is either administered in combination with paclitaxel for women who have not previously undergone chemotherapy, or used alone as a follow-up treatment for patients whose disease was unresponsive to previous chemotherapy treatments.
ECRI, originally an abbreviation for Emergency Care Research Institute, is an independent nonprofit health services research agency. The organization is a Collaborating Center for health care technology assessment of the World Health Organization and has been designated an Evidence-based Practice Center by the US Agency for Healthcare Research and Quality.
The organization's report addressed four key issues in determining the effectiveness and safety of the drug: overall patient survival rates, quality of life, tumor response rate, and time-to-disease progression. The research included comprehensive literature searches for all published studies and use of predetermined criteria to select and analyze studies.
One of the trials selected for analysis compared trastuzumab plus chemotherapy with chemotherapy alone for metastatic breast cancer, and the other compared two different doses of trastuzumab alone for metastatic breast cancer.
Evidence suggests that increasing the dosage beyond the standard had little or no impact on the effectiveness. The available evidence is currently insufficient to determine the safety or efficacy of trastuzumab for early-stage (i.e., Stage I or II) breast cancer or as an adjuvant therapy, but several clinical trials are in progress to assess the drug's effectiveness for these patients.